19" and "hypoxemia" are entered in a cursory PubMed search, yet a quantitative understanding of the functional impairment leading to hypoxemia during COVID-19 has not been established. In this issue of Anesthesiology, Busana et al. 1 provide novel data on fundamental physiologic factors producing hypoxemia in patients with COVID-19 acute respiratory distress syndrome (ARDS) using two sophisticated methods to study respiratory physiology: the multiple inert gases elimination technique (MIGET) combined with imaging data from dual-energy computed tomography (DECT).Early in medical school, we learn that the four physiologic determinants of hypoxemia are hypoventilation, diffusion impairment, right-to-left shunt, and alveolar ventilation to perfusion ( VA / QT ) mismatch. 2 For comprehensiveness, diffusion-to-perfusion mismatch can be added as a fifth. 3,4 We further learn that VA / QT mismatch is the predominant cause of gas exchange Image: A. Johnson, Vivo Visuals Studio. This editorial accompanies the article on p. 251. This article has a related Infographic on p. A17. This article has an audio podcast.